Abstract
Multidrug resistance, MDR, is a major obstacle in the chemotherapeutic treatment of cancer. MDR can be reversed by drugs that vary widely in their chemical structure and main biological action. Many efforts are directed to find out the relationships between the structure and MDR reversal effect of these drugs. In this review we try to summarize the results of a variety of studies on identification of structure-activity relationships, SARs, and quantitative SARs, QSARs, of different MDR reversing drugs. As any reasonable (Q)SAR study relies on a real or putative presenta-tion about the mechanism of action of the studied compounds, the most significant MDR mechanisms revealed till now are shortly discussed. Special attention is paid to P-glycoprotein, P-gp, related MDR as the most experimentally and clinically tested form of drug resistance. The currently proposed models of P-gp functioning and mechanisms of MDR modulation are presented. Problems that can arise in (Q)SARs studies are discussed in advance to allow the reader to judge on possible pitfalls. The physicochemical and structural properties of MDR modulators as found by different research groups are commented and summarized. From the discussed studies it can be concluded that the careful selection of relevant structural and biological data processed with appropriate QSAR and especially 3D-QSAR methods, is a promising approach to structure-activity studies of MDR reversers.
Keywords: Multidrug Resistance Reversers, MRP, Paclitaxd, Virblastine, Etopside, Mitomycine, DNA topoisomerases MDR, Almitrine, Lung resistance protein MDR, Drug Uptake
Current Medicinal Chemistry
Title: Structure-Activity Relationships of Multidrug Resistance Reversers
Volume: 8 Issue: 6
Author(s): Michael Wiese and Ilza K. Pajeva
Affiliation:
Keywords: Multidrug Resistance Reversers, MRP, Paclitaxd, Virblastine, Etopside, Mitomycine, DNA topoisomerases MDR, Almitrine, Lung resistance protein MDR, Drug Uptake
Abstract: Multidrug resistance, MDR, is a major obstacle in the chemotherapeutic treatment of cancer. MDR can be reversed by drugs that vary widely in their chemical structure and main biological action. Many efforts are directed to find out the relationships between the structure and MDR reversal effect of these drugs. In this review we try to summarize the results of a variety of studies on identification of structure-activity relationships, SARs, and quantitative SARs, QSARs, of different MDR reversing drugs. As any reasonable (Q)SAR study relies on a real or putative presenta-tion about the mechanism of action of the studied compounds, the most significant MDR mechanisms revealed till now are shortly discussed. Special attention is paid to P-glycoprotein, P-gp, related MDR as the most experimentally and clinically tested form of drug resistance. The currently proposed models of P-gp functioning and mechanisms of MDR modulation are presented. Problems that can arise in (Q)SARs studies are discussed in advance to allow the reader to judge on possible pitfalls. The physicochemical and structural properties of MDR modulators as found by different research groups are commented and summarized. From the discussed studies it can be concluded that the careful selection of relevant structural and biological data processed with appropriate QSAR and especially 3D-QSAR methods, is a promising approach to structure-activity studies of MDR reversers.
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Cite this article as:
Wiese Michael and Pajeva K. Ilza, Structure-Activity Relationships of Multidrug Resistance Reversers, Current Medicinal Chemistry 2001; 8 (6) . https://dx.doi.org/10.2174/0929867013373138
DOI https://dx.doi.org/10.2174/0929867013373138 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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